Structure and Functions of Gap Junctions and Their Constituent Connexins in the Mammalian CNS

E Yu Kirichenko,S N Skatchkov,A M Ermakov

doi:10.1134/s1990747821020069

E Yu Kirichenko, S N Skatchkov + Show 1 more

Open Access

https://doi.org/10.1134/s1990747821020069

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Abstract

—Numerous data obtained in the last 20 years indicate that all parts of the mature central nervous system, from the retina and olfactory bulb to the spinal cord and brain, contain cells connected by gap junctions (GJs). The morphological basis of the GJs is a group of joined membrane hemichannels called connexons, the subunit of each connexon is the protein connexin. In the central nervous system, connexins show specificity and certain types of them are expressed either in neurons or in glial cells. Connexins and GJs of neurons, combining certain types of inhibitory hippocampal and neocortical neuronal ensembles, provide synchronization of local impulse and rhythmic activity, thalamocortical conduction, control of excitatory connections, which reflects their important role in the processes of perception, concentration of attention and consolidation of memory, both on the cellular and at the system level. Connexins of glial cells are ubiquitously expressed in the brain, and the GJs formed by them provide molecular signaling and metabolic cooperation and play a certain role in the processes of neuronal migration during brain development, myelination, tissue homeostasis, and apoptosis. At the same time, mutations in the genes of glial connexins, as well as a deficiency of these proteins, are associated with such diseases as congenital neuropathies, hearing loss, skin diseases, and brain tumors. This review summarizes the existing data of numerous molecular, electrophysiological, pharmacological, and morphological studies aimed at progress in the study of the physiological and pathophysiological significance of glial and neuronal connexins and GJs for the central nervous system.

Highlights

Gap junction, or nexus, is the conductive type of cell-to-cell contact providing direct transition of small water-soluble molecules with a molecular weight of no more than 1.5 kDa from the cytoplasm of one cell into the cytoplasm of another cell
As we have shown in the previous studies of the cerebral cortex and the olfactory bulb, connexin 30 (Cx30) is concentrated mostly in fine astrocyte branches around microcapillaries and vessels
The research on the structure, functions, lifecycle of gap junctions (GJs) and the proteins composing them in the cells of living organisms under normal and pathological conditions has aroused interest in the past 50 years, and the amount of these studies continues to increase

Summary

INTRODUCTION

Nexus, is the conductive type of cell-to-cell contact providing direct transition of small water-soluble molecules with a molecular weight of no more than 1.5 kDa (inorganic ions, sugars, amino acids, nucleotides, vitamins, etc.) from the cytoplasm of one cell into the cytoplasm of another cell. Hereditary mutations in the GJB2 gene of connexin 26 are a basis of mutilation syndromes of sensorineural deafness, hearing loss and hyperkeratosis with autosomal recessive (DFNB1) and autosomal dominant (DFNA3) types of inheritance [104, 105] These mutations have been described as missense mutations, which result in nonconservative amino acid substitution, impaired function of extracellular loop EL1 of the Cx26 molecule, and inability of the protein to form connexons and GJs. more and more cases of combination of the above-described syndrome and the Dandy–Walker malformation are described [106] and, the GJB2 gene is supposed to be involved in other, similar to this malformation, hereditary diseases of known and unknown etiology. It is known that pannexins play an important biological role as the components of hemichannels, favoring the release of ATP and modulating the intercellular propagation of calcium waves [115]

CONCLUSIONS

Findings

COMPLIANCE WITH ETHICAL STANDARDS